Since it would be impossible to conduct various research protocols on humans, a more practical alternative would be to obtain an animal model which can be studied safely which provides many of the characteristics of the human juvenile diabetes. The selected animals should mimic, as much possible, the human diabetes disease. Several such models exist and provide an opportunity to evaluate etiologic concepts and possible therapeutic modalities. The three animal models which fulfill at least one important observation, namely, the presence of insulitis (lymphocyte infiltration around the beta cells) are: 1) EMC-virus M- variant induced diabetes in mouse; 2) the streptozotocin-induced insulitis model; and 3) the "BB" rat. Of these three experiments, the streptozotocin-induced insulitis and "BB" rats are presently being investigated in our laboratory. Streptozotocin-Induced Insulitis: The administration of one small dose of streptozotocin causes mild degranulation of the beta cells during the first 72 hours, but no hyperlgycemia. However, five subdiabetogenic doses of streptozotocin injected intravenously or intraperitoneally into CD-1 mouse produces a delayed but progressive increase in blood glucose with levels greater than 350 mg% attained by five to six days after the last injection. Histologic examination of the pancreatic islets reveals pronounced insulitis with infiltrating lymphocytes and macrophages. With electron microscopy, the induction of a Type-C virus within the surviving beta cells has also been observed. Over the past few years, our laboratory has attempted to evaluate three aspects of the syndrome, namely, the induction of the Type-C virus; direct toxicity of streptozotocin; and the cell-mediated immune component.